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Description of key information

Oral: based on a weight of evidence approach, all oral repeated dose toxicity studies for the test substance revealed no adverse effects.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises studies which each alone are regarded insufficient for assessment (Klimisch score 4). However, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with
Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated oral dose toxitcity

A weight of evidence approach based on data for sorbitan monolaurate, ethoxylated (<2.5 EO, Polysorbate 21, CAS 9005-64-5) together with data on sorbitan monolaurate, ethoxylated (20 EO, Polysorbate 20, CAS 9005-64-5) was performed since data on oral repeated dose toxicity is limited for Polysorbate 21. Repeated dose toxicity after oral exposure to Polysorbate 21 was investigated in a chronic life-span feeding study (104 wks) with rats at a concentration of 2% in diet, corresponding to 2000 mg/kg bw/d (calculation based on the assumption of an average body weight of 200 g and an average food consumption of 20 g/animal) (Croda 1949). In the test group, 30 male animals were included whereas 50 animals served as control. Mortality, clinical signs of toxicity and body weight development of the experimental group were comparable to controls. Haematology, clinical chemistry, gross pathology and histopathology did not reveal differences between test and control animals. Therefore, the NOAEL for male rats was determined to be >2000 mg/kg bw/day. In a second study, oral administration of Polysorbate 20 via food was investigated in a sub-chronic study with 25% test substance in 10 male rats, corresponding to 25000 mg/kg bw/day (calculated on the assumption of an average body weight of 200 g and an average food consumption of 20 g/animal) (Eagle 1956). Diarrhea was observed in all treated animals. One animal died (group not specified). No effects on body weight development were observed in the experimental group. At gross pathology, unusual high incidences of renal hypertrophy, renal/urinary bladder calculi, ulceration of the tail, enlargement of caecum and spleen, small testes and ulceration in the stomach were observed in the test substance treated animals. Histopathology further revealed microscopic alterations in kidney, testes, lymphoid tissue, liver, intestinal tract and coronary tissues in the treated animals. With regard to these results, a LOAEL of 25000 mg/kg bw/day was set for male rats. In another study, polysorbate 20 was orally administered via food to male and female rats (14 males and 16 females/group) daily for 70 days (Harris 1951). At the beginning, 5% test substance was administered and the dose was increased to 25% during the first 10 days, corresponding to 5000 (5%) and 25000 (25%) mg/kg bw/day, based on the assumption of an average body weight of 200 g and an average food consumption of 20 g/animal. 5 experimental animals died during the study. Test substance treated animals developed diarrhea during the first week which later became so severe that the tail became inflamed. Body weight gain was reduced to 67% of controls. In relation, food consumption and food efficiency was less when compared to controls. No effects on organ weights were observed. At gross pathology, a majority of rats fed the test substance revealed distended caeca filled with liquid and gas. At histopathology, effects on the gastrointestinal tract, kidneys and spleens, lungs, testes and ovaries were observed. Therefore, a LOAEL of 25000 mg/kg bw/day was determined for both genders. In addition, a study performed with polysorbate 20 in hamsters is available (Eagle 1956). Animals (10/group) were treated with 5, 10 and 15% test substance concentrations for up to 39 weeks by gavage (corresponding to 3750, 7500, 11250 mg/kg bw/day; calculated on the assumption of an average body weight of 200 g and an average food consumption of 15 g/animal). Mortalities in the experimental groups were observed as follows: 1/10, 2/10, 1/10 for the 3750, 7500, 11250 mg/kg bw/day dose groups. Most of the experimental animals showed diarrhea. At gross pathology small testes, large/distended caeca as well as very pale and distorted/granular kidneys suggestive of nephrosclerosis were dose-dependently observed in the experimental animals. At histopathology, hemosiderosis and cirrhosis in the liver as well as obstructive nephropathy, pyelonephritis and atrophy in the kidney was observed from the 3750 mg/kg bw/day dose level onwards. Therefore, a LOAEL of 3750 mg/kg bw/day was determined for hamsters from the results of this study.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is based on the weight of evidence from all available studies.

Justification for classification or non-classification

The available data on repeated dose toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.